Evidence map›Paper›PMID 38112569›Full record

ArticleCerebral cortex (New York, N.Y. : 1991)2024

The interaction effects of age, APOE and common environmental risk factors on human brain structure.

Jie Chen, Tengfei Li, Bingxin Zhao, Hui Chen, Changzheng Yuan, Gwenn A Garden, Guorong Wu, Hongtu Zhu

Abstract read
In one paragraph

Article in Cerebral cortex (New York, N.Y. : 1991), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Alcohol use andAlzheimer's & dementia. Behavior & socioeconomics of aging · 2026
    Article
  3. Article
  4. Review
  5. Article
  6. Atherosclerotic features in patients with heart failure.Archives of medical science : AMS · 2025
    Article
  7. Article
  8. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Jie ChenDepartment of Biostatistics, University of North Carolina at Chapel Hill, 135 Dauer Drive, Chapel Hill NC 27514, United States.
Tengfei LiDepartment of Radiology, School of Medicine, University of North Carolina at Chapel Hill, 101 Manning Drive, Chapel Hill, NC 27514, United States.
Bingxin ZhaoDepartment of Statistics and Data Science, The Wharton School, University of Pennsylvania, 265 South 37th Street, 3rd & 4th Floors, Philadelphia, PA 19104-1686, United States.
Hui ChenSchool of Public Health, Zhejiang University School of Medicine, 866 Yuhangtang Rd, Hangzhou 310058, China.
Changzheng YuanSchool of Public Health, Zhejiang University School of Medicine, 866 Yuhangtang Rd, Hangzhou 310058, China.
Gwenn A GardenDepartment of Neurology, School of Medicine, University of North Carolina at Chapel Hill, 170 Manning Drive Chapel Hill, NC 27599-7025, United States.
Guorong WuDepartment of Psychiatry, School of Medicine, University of North Carolina at Chapel Hill, 101 Manning Drive, Chapel Hill, NC 27514, United States.
Hongtu ZhuDepartment of Biostatistics, University of North Carolina at Chapel Hill, 135 Dauer Drive, Chapel Hill NC 27514, United States.

Funding

Mapping the Causal Genetic-Imaging-Clinical Pathway for Alzheimer's DiseaseRF1AG082938 · NIA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Bingxin Zhao, Hongtu Zhu · 2023 to 2026
$3.6M
Analysis of Big Data Squared in Biomedical StudiesR01MH116527 · NIMH · YALE UNIVERSITY · PI ZHANG, HEPING · 2018 to 2022
$2.3M
A Scalable Platform for Exploring and Analyzing Whole Brain Tissue Cleared ImagesR01NS110791 · NINDS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI WU, GUORONG · 2019 to 2023
$1.9M
NIA NIH HHS RF1 AG082938NIA NIH HHS RF1AG082938NIH HHS MH116527NINDS NIH HHS R01 NS110791
6 · The paper itself

Abstract

Mounting evidence suggests considerable diversity in brain aging trajectories, primarily arising from the complex interplay between age, genetic, and environmental risk factors, leading to distinct patterns of micro- and macro-cerebral aging. The underlying mechanisms of such effects still remain unclear. We conducted a comprehensive association analysis between cerebral structural measures and prevalent risk factors, using data from 36,969 UK Biobank subjects aged 44-81. Participants were assessed for brain volume, white matter diffusivity, Apolipoprotein E (APOE) genotypes, polygenic risk scores, lifestyles, and socioeconomic status. We examined genetic and environmental effects and their interactions with age and sex, and identified 726 signals, with education, alcohol, and smoking affecting most brain regions. Our analysis revealed negative age-APOE-ε4 and positive age-APOE-ε2 interaction effects, respectively, especially in females on the volume of amygdala, positive age-sex-APOE-ε4 interaction on the cerebellar volume, positive age-excessive-alcohol interaction effect on the mean diffusivity of the splenium of the corpus callosum, positive age-healthy-diet interaction effect on the paracentral volume, and negative APOE-ε4-moderate-alcohol interaction effects on the axial diffusivity of the superior fronto-occipital fasciculus. These findings highlight the need of considering age, sex, genetic, and environmental joint effects in elucidating normal or abnormal brain aging.

Indexed as

Alzheimer DiseaseApolipoprotein E4AgingApolipoproteins EBrainFemaleGenotypeHumansRisk FactorsApoE protein, humanApolipoprotein E4Apolipoproteins EAlzheimer’s diseaseAPOEbrain agingDTI & ROI volumeslifestyle

Identifiers

PMID38112569
PMCPMC10793588

What OpenQuestion holds

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Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.